Neuropsychiatric Complications of Hepatitis C and Its Treatment
July 1, 2000
Neuropsychiatric Complications of Hepatitis C and Its Treatment
Abstract & commentary
Source: Dieperink E, et al. Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: A review. Am J Psychiatry 2000;157:867-876.
The hepatitis c virus is widespread, often clinically silent, and is occasionally deadly. Hepatitis C infection itself, and more commonly its treatment with interferon alpha, may cause disabling, even lethal psychiatric symptoms. Dieperink and colleagues review summarize the available research findings in this area.
Hepatitis C infection is most often associated with intravenous drug use, blood transfusion prior to the advent of effective screening of blood donors for the virus, alcoholic liver disease, multiple sexual partners, and needlestick injuries among health workers. Once infected, 85% of patients will develop chronic hepatitis, and one in five of these chronically infected individuals will progress to cirrhosis. Excessive alcohol consumption appears to worsen the long-term prognosis of hepatitis C infection.
The major neuropsychiatric complication of hepatitis C infection appears to be a slightly higher risk of depressive symptoms and major depression. In these studies, it is difficult to disentangle the effects of the hepatitis C virus itself from the higher rate of depression among the patient groups at risk for hepatitis C exposure (e.g., intravenous drug abusers).
Currently, the major treatment for hepatitis C is parenteral treatment with interferon alpha. The interferons are a class of peptides within a larger group of immune modulators known as cytokines. Unfortunately, the use of interferon alpha monotherapy in hepatitis C cannot be called a major success, since only about 40% of patients respond favorably to the treatment. In addition, the vast majority of hepatitis C patients will relapse after discontinuing interferon alpha. Newer treatment combinations appear to be more successful. For example, the combination of interferon alpha with the antiviral agent ribavirin is more effective than using interferon alpha alone.
The neuropsychiatric side effects of interferon alpha are well documented. These neuropsychiatric reactions can be divided into acute effects and subacute or chronic effects. Acutely, interferon alpha produces a flu-like syndrome in the majority of patients. After several weeks of treatment, interferon alpha frequently causes fatigue, malaise, insomnia, apathy, cognitive dysfunction, depressed mood, and anxiety. The frequency of clinically significant depressive symptoms has ranged from 3% to 57%, depending on the study methodology. For example, the most rigorously designed studies using standard rating scales for depression and a prospective design reported rates of major depression of about 20-40%. Less well-designed studies using self-rated scales or more general rating scales that treated "depression" as a single item generally observed consistently lower rates of major depression. Interestingly, a family history of depressive illness or prior personal history of major depression did not predict who would become depressed during treatment with interferon alpha.
Fatigue is the neuropsychiatric symptom that occurs most frequently during interferon alpha therapy. Unlike some of the other side effects, the fatigue often persists or worsens with ongoing treatment. Other neuropsychiatric symptoms have also been reported, but at a lower frequency. For example, irritability, mood lability, anxiety, and rarely mania and psychosis have all been observed.
Comment by Andrew L. Stoll, MD
Several treatment options are available for neuropsychiatric symptoms emerging during treatment with interferon alpha. Unfortunately, no controlled data exist regarding treatment of interferon alpha induced neuropsychiatric symptoms. Serotonin reuptake inhibitors and the opiate antagonist naltrexone have been used and, at least anecdotally, are effective. Although not mentioned in the article, other options to consider would be nootropic and energizing agents, such as psychostimulants and modafanil (Provigil), as well as the nonsedating antidepressant bupropion (Wellbutrin SR).
As hepatitis C grows in prevalence, the importance of the neuropsychiatric complications of the virus itself, particularly with interferon alpha therapy, will be amplified. More study into the pathophysiological mechanism(s) underlying the neuropsychiatric adverse effects of interferon alpha will hopefully yield improved treatment of these serious complications. In the meantime, using conventional psychopharmacological tools targeted to specific symptoms will likely be useful and will permit treatment with interferon alpha therapy in more patients for a longer duration of time.
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